Influence of factor VIII/von Willebrand factor protein (F VIII/vWF) and F VIII/vWF-poor cryoprecipitate on post-ischemic microvascular reperfusion in the central nervous system.
To test the hypothesis that plasma contains native constituents capable of impairing microcirculatory flow in zones of acute ischemic tissue damage, we performed 14C-antipyrine autoradiographic blood flow studies in splenectomized dogs subjected to 35 min of cerebrospinal fluid compression ischemia followed by 30 min of recirculation to the neuraxis. The animals were anticoagulated with heparin and were divided into 4 groups by exposure to various measures before induction of ischemia. Groups 1 and 2 served for comparison with the other groups and underwent, respectively, no glass-wool filtration and glass-wool filtration via an arteriovenous shunt. Post-ischemic brain blood flows in Group 1 were low and focal zones of greatly impaired reperfusion were present. In Group 2, post-ischemic brain blood flows were high and focal perfusion impairment did not occur. Group 3 received homologous purified factor VIII/von Willebrand factor protein (F VIII/vWF) after glass-wool filtration but before induction of ischemia; Group 4 received F VIII/vWF-poor cryoprecipitate at the same time point. The purpose of administering the plasma preparations was to check for the presence of activity that nullified the enhancement of post-ischemic reperfusion expected after exposure to glass-wool. The results indicate that activity deleterious to post-ischemic reperfusion primarily resides in the F VIII/vWF fraction of cryoprecipitate. The F VIII/vWF-poor cryoprecipitate infusate, containing 250 to 800-fold more protein than the F VIII/vWF fraction, produced an intermediate reduction of blood flow.
D000818:Animals; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001794:Blood Pressure; D002545:Brain Ischemia / Q000503:physiopathology*; D002490:Central Nervous System / Q000098:blood supply; D011232:Chemical Precipitation; D003450:Cryoglobulins / Q000494:pharmacology*; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D005169:Factor VIII / Q000494:pharmacology*; D006467:Hemophilia A / Q000503:physiopathology; D008297:Male; D008833:Microcirculation; D010477:Perfusion; D014842:von Willebrand Diseases / Q000503:physiopathology; D014841:von Willebrand Factor / Q000494:pharmacology*
D001779:Blood Coagulation Factors; D003450:Cryoglobulins; D014841:von Willebrand Factor; D005169:Factor VIII